Water → tert-butyl (1R,2R)-1-(6-bromopyridin-2-yl)-2-hydroxy-2-(3-methoxyphenyl)ethylcarbamate

Temperature

50 °C

To a solution of tert-butyl carbamate (109 mg, 0.931 mmol) in acetonitrile (5 mL) at 0° C. was added tert-butyl hypochlorite (0.105 mL, 0.93 mmol). After stirring for 5 min, the reaction was treated with silver oxide (108 mg, 0.465 mmol). After stirring for 10 min, the resulting suspension was treated with (E)-2-bromo-6-(3-methoxystyryl)pyridine (180 mg, 0.620 mmol), osmium tetroxide (0.1 mL, 0.32 mmol), and water (0.025 mL, 1.37 mmol). The ice bath was removed and stirring continued for 8 h. The reaction was filtered and treated with a solution of sodium sulfite (5% in water, 1.5 mL). The resulting solution was heated to 50° C. and held there for 8 h. The reaction was cooled to room temperature and diluted with ethyl acetate. The organics were washed with water, then brine, dried over magnesium sulfate, concentrated, and purified by column chromatography (25% EtOAc/Hex). HNMR of the purified material suggested that it was ca. 1:1 mixture of regioisomers. The product (114 mg, 43%) was used as a mixture of regioisomers. Mass spec.: 423.09 (MH)+.

1. stirringAfter stirring for 10 min
2. customThe ice bath was removed
3. stirringstirring
4. waitcontinued for 8 h
5. filtrationThe reaction was filtered
6. additiontreated with a solution of sodium sulfite (5% in water, 1.5 mL)
7. waitheld there for 8 h
8. temperatureThe reaction was cooled to room temperature
9. additiondiluted with ethyl acetate
10. washThe organics were washed with water
11. dry with materialbrine, dried over magnesium sulfate
12. concentrationconcentrated
13. custompurified by column chromatography (25% EtOAc/Hex)
14. addition1:1 mixture of regioisomers
15. additionThe product (114 mg, 43%) was used as a mixture of regioisomers

ORD record

ord-aa32ac152a7845c191e956e6790b8457

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691821B2